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Takeshi Kanagawa

Publications and source records attributed to Takeshi Kanagawa.

13 recordsLinked to original sources

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.

Animals↗

A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat.

Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not only adults but also neonates. However, the side effects of hypothermia in the developing brain, where a massive amount of neurogenesis occurs, remain unclear. We investigated the proliferation of neural progenitor cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats in a severe hypothermic environment. The rat pups were divided into two groups, a hypothermia group (30 degrees C: n=10) and a normothermia group (37 degrees C: n=10). After the pups were placed for 21 h in each environment, 100 mg/kg/day of BrdU was injected intraperitoneally to label dividing cells, and then the pups were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the subventricular zone of the periventricle and the subgranular zone of the dentate gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased in number in the dentate gyrus, but not in the periventricular region. Thus, the severe hypothermic environment induced a decrease of neurogenesis in the neonatal rat. These observations are noteworthy regarding clinical hypothermia therapy following cerebral hypoxic ischemic injury during the perinatal period.

Aging↗

Long-term neuroprotective effects of carbon dioxide on neonatal rat hypoxic-ischemic brain injury: an experimental study of skilled motor tasks.

OBJECTIVE: This study was undertaken to investigate the long-term effect of hypercapnia on neonatal hypoxic-ischemic brain injury, we tested its effect in a neonatal rat hypoxia-ischemia model. STUDY DESIGN: The rats were subjected to unilateral carotid artery ligation and exposure to 8% oxygen for 30 minutes. Six percent carbon dioxide was administered to the neonatal rats during unilateral hypoxia-ischemia, and the motor function and neurologic outcomes were determined 3 months later. RESULTS: Significant motor functional improvement was observed in the hypercapnic animals, as judged by the Montoya staircase test. The unilateral brain injury was significantly ameliorated in the hypercapnic animals, and this amelioration was well correlated with the motor functional performance. Cerebral blood flow during hypoxia-ischemia, monitored by laser Doppler flowmetry, was better preserved in the hypercapnic animals. CONCLUSION: Our results suggest that mild hypercapnia during hypoxia-ischemia may provide long-lasting motor functional as well as neurologic protection for immature brains, possibly by increasing cerebral blood flow during hypoxia.

Animals↗

The effects of repeated corticosteroid administration on the neurogenesis in the neonatal rat.

OBJECTIVE: The purpose of this study is to clarify the effects on the brain including neurogenesis pretreated with repeated doses of dexamethasone in the neonatal rat. STUDY DESIGN: The 4-day-old Sprague Dawley rats were pretreated with 4 different regimens, namely, single administration of dexamethasone, 2-dose administration, 3-dose administration, and saline administration as a control. Concurrently, bromodeoxyuridine (BrdU), which was incorporated into the dividing cells, was administered. We examined body weight, brain weight, and the number of BrdU-labeled cells in the subventricular zone (SVZ), the subgranular zone (SGZ), and the cortex. RESULTS: Both the body and brain weight of the rats pretreated with dexamethasone were significantly decreased compared with those given saline. Quantitative analysis of BrdU-labeled cells revealed the significant dose-dependent decreases in the SVZ, the SGZ, and the cortex with the dexamethasone treatment. CONCLUSION: We concluded that the decreases in neurogenesis caused by repeated antenatal corticosteroid therapy might result in the adverse effects on the size of the head at birth.

Aging↗

Prospective study of non-closure or closure of the peritoneum at cesarean delivery in 124 women: Impact of prior peritoneal closure at primary cesarean on the interval time between first cesarean section and the next pregnancy and significant adhesion at second cesarean.

AIM: The aim of this study was to evaluate the effect of non-closure of the peritoneum at cesarean delivery on postoperative complications and the interval time to the next pregnancy, and to investigate the incidence of adhesion following cesarean and the association between adhesion formation and peritoneal closure. METHODS: One hundred and twenty four women scheduled for cesarean section were randomized to either closure of both the visceral and parietal peritoneum (C-group, n = 70) or non-closure (NC-group, n = 54). At repeated cesarean, the levels and extent of adhesion, operating time, and any complications were examined. RESULTS: There was no difference in the incidence of postoperative complications at the first cesarean section. The operating time of the C-group was significantly longer than that of the NC-group. The frequency of analgesic use was significantly higher in the C-group. The time interval from cesarean section to the next pregnancy in the NC-group was significantly shorter than that in the C-group. There are no significant differences between the rates of complications in the C-group and the NC-group at repeated cesarean. The incidence of adhesion in the C-group was significantly higher than that in the NC-group (P < 0.05). The mean total operating time and the mean interval time for skin incision to delivery in the C-group were significantly longer than those in the NC-group (P < 0.05 and P < 0.001, respectively) at repeated cesarean section. CONCLUSIONS: Non-closure of the peritoneum at cesarean delivery appears to have no adverse effect on postoperative recovery, it also decreases the number of analgesic doses and shortens the operating time and may be more desirable in achieving a next pregnancy. The present study demonstrated that surgical peritoneal closure resulted in more advanced adhesion formation. The practice of non-closure of the peritoneum should be performed at cesarean.

Adult↗

Reduction of aquaporin-8 on fetal membranes under oligohydramnios in mice lacking prostaglandin F2 alpha receptor.

AIM: To investigate the association between aquaporin-8 (AQP-8: a water channel protein) expression in fetal membranes and oligohydramnios during near-term and postdate pregnancy, we set up an oligohydramnios model using prostaglandin F2 alpha receptor (FP)-deficient mice. METHODS: Pregnant FP-deficient mice from 14 to 21 gestational days (GD) were killed to measure the amniotic fluid volume (AFV), and fetal membranes were collected for the analysis of aquaporin-8 expression. RESULTS: The AFV was highest at 14 GD, and was significantly decreased to 28% and 0% at 20 GD and 21 GD, respectively, compared with the volume at 14 GD. Immunohistochemistry and immunoblot analysis showed that aquaporin-8 was expressed in the basal component of fetal membranes, and that the protein level was significantly decreased to 60% at 20 GD compared with that at 14 GD. CONCLUSIONS: We demonstrated that AQP-8 expression in the fetal membrane was decreased at post term in FP-deficient mice. Our findings suggest that aquaporin-8 in fetal membranes may be involved in the regulation of AFV, especially when oligohydramnios occurs.

Amniotic Fluid↗

Mid-second trimester measurement of fetal nasal bone length in the Japanese population.

AIM: We carried out a preliminary study to compare the nasal bone length (NBL) and biparietal diameter/NBL (BPD/NBL) ratio between the Japanese and white populations. METHODS: Three hundred and fifty nine (359) singleton fetuses of healthy Japanese couples were examined from June 2004 to October 2005. NBL was measured by the strict midsagittal section. The reference range of NBL was established from cross-sectional data between 15 and 25 weeks' gestation. RESULTS: The success rate of obtaining reliable NBL was 93% (333/356). There were 330 fetuses (93%) available for constructing a reference range from the population. The median NBL increased from 3.2 mm at 15 weeks' to 7.6 mm at 25 weeks' gestation. The median of BPD/NBL ratio was 9.01. CONCLUSIONS: We demonstrated that NBL was significantly shorter and BPD/NBL was significantly greater in the Japanese population than those in the white and black populations.

Adolescent↗

Expression of fractalkine in the Fallopian tube and of CX3CR1 in sperm.

BACKGROUND: Fractalkine is a CX(3)C chemokine that has chemoattractant activity for T cells, monocytes and natural killer (NK) cells. The objective of this study was 2-fold: to evaluate (i) the presence of fractalkine in the Fallopian tube and (ii) the existence of CX(3)CR1 (fractalkine receptor) in ejaculated sperm. METHODS AND RESULTS: Western blot analysis revealed that fractalkine protein was detected as a 95 kDa band in the isthmus, the ampulla and the infundibulum of the Fallopian tube. Immunohistochemistry revealed positive staining of epithelial cells in the Fallopian tube. RT-PCR demonstrated that fractalkine transcripts were expressed in all parts of the Fallopian tube. RT-PCR also revealed that CX(3)CR1-positive cells were present in the Fallopian tube. CX(3)CR1-positive cells were present in the stroma of the Fallopian tube. The villi of the ciliated cells were positively stained. To determine the function of fractalkine in the Fallopian tube, we examined whether CX(3)CR1 was present in ejaculated sperm. RT-PCR demonstrated that CX(3)CR1 transcripts were expressed in the ejaculated sperm. Immunohistochemistry demonstrated positive staining of the tail of the spermatozoa. CONCLUSIONS: The present findings suggest that fractalkine in the Fallopian tube contributes to the immunodefence mechanism during fertilization and to the sperm motion in the oviduct.

Adult↗

Effects of hyperthermia on hypoxic-ischemic brain damage in the immature rat: its influence on caspase-3-like protease.

OBJECTIVE: Recent clinical studies suggested that intrapartum maternal fever is a strong independent risk factor for neonatal encephalopathy. With use of a well-studied rat model of neonatal hypoxic-ischemic encepalopathy, this study investigated the hypothesis that intraischemic hyperthermia accelerates and worsens brain injury in immature animals and examined whether apoptotic cell death machinery is involved in the underlying mechanisms. STUDY DESIGN: Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% oxygen for 15 minutes (n = 32 rats). During the 15-minute hypoxic insult, body temperature was elevated to 40 degrees C in 16 animals (hyperthermic hypoxic insult group), and was maintained at 37 degrees C in 16 animals (normothermic hypoxic insult group). Then both groups were placed in the same chamber in a water bath at 37 degrees C for 24 hours and finally returned to the mothers. Caspase-3-like activity was assessed 36 hours after the hypoxic-ischemic insult. One week later, microtubule-associated protein-2 immunostaining was used to examine neuronal damage. RESULTS: Intraischemic hyperthermia was shown to activate the caspase-3 activity 36 hours after hypoxia-ischemia while caspase-3 was activated insignificantly in the normothermic hypoxic insult group at that time. The hyperthermic hypoxic insult group also showed a reduced microtubule-associated protein-2-positive area 7 days after hypoxia-ischemia compared with that in the normothermia group. CONCLUSION: Hyperthermia during hypoxia-ischemia makes the immature brain inordinately susceptible to hypoxic-ischemic insult and causes brain injury, even if hypoxic-ischemic insult is so mild that it causes no or little injury by itself. This effect may be mediated by the escalation of the apoptotic cell death pathway in the immature animal.

Animals↗

Postischemic hyperthermia induced caspase-3 activation in the newborn rat brain after hypoxia-ischemia and exacerbated the brain damage.

The effects of postischemic hyperthermia were investigated in the newborn rat brain after hypoxia-ischemia (HI). Seven-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 30 min, and divided into a hyperthermia group (rectal temperature at 39 degrees C for 6 h) and a normothermia group. Hyperthermia resulted in an approximately 5-fold increase in activated caspase-3 24 h after HI when compared with the normothermia group, and gross loss of brain tissue was observed only in the hyperthermia group at 7 and 30 days after HI. Our results show that postischemic hyperthermia exacerbates HI injury in immature brains, and that the mechanism is strongly associated with activation of an apoptotic pathway.

Animals↗

Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats, assessed by auditory brainstem response.

A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats were divided into three groups: hypothermia group (n = 6), normothermia group (n = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia group, but was kept at 37 degrees C in the normothermia and sham control group. Three months later the rats were assessed by auditory brainstem response, then killed. The normothermia group showed increased III-V latencies and wave V abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologically correlated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermia may provide effective and long-lasting neurofunctional as well as histopathologic protection to the immature brain.

Animals↗

Fetal atrial flutter recorded prenatally by magnetocardiography.

A case of fetal atrial flutter successfully recorded by magnetocardiography (MCG) is reported. Initial ultrasonography revealed frequent fetal atrial extrasystoles at 31 weeks of gestation. Fetal MCG was recorded using a multichannel MCG system at 31, 35 and 38 weeks of gestation. A series of fluctuations in the baseline of the MCG were noted at 35 and 38 weeks of gestation, which were revealed to be atrial flutter P waves. The averaged MCG showed that the fetal arrhythmia was an atrial flutter with a 3:1 atrioventricular block. The diagnosis was confirmed by neonatal electrocardiogram. Fetal MCG may be useful for the diagnosis of fetal atrial flutter.

Adult↗

The coincidence of fetal magnetocardiography and direct electrocardiography in a case of fetal atrial flutter due to intracardiac tumor.

OBJECTIVE: To demonstrate the coincidence of fetal magnetocardiography (FMCG) and fetal direct electrocardiography (FDECG) in a case of fetal atrial flutter (AF). METHODS: FMCG and FDECG using a fetal scalp electrode were recorded in the case of fetal AF at 41 weeks' gestation. RESULTS: FMCG revealed fetal AF with 2:1 atrioventricular block, which was also documented by FDECG using a fetal scalp electrode. The prenatal diagnosis was confirmed by postnatal electrocardiogram. Neonatal echocardiography revealed an intracardiac tumor on the left atrial septum. The tumor seemed to be the cause of AF. CONCLUSION: FMCG may provide the same information as a fetal electrocardiogram in the prenatal diagnosis of fetal AF.

Adult↗